Nilotinib (4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide), is a small molecule tyrosine kinase inhibitor that has been approved for treatment of chronic myelogenous leukemia (CML). In particular, this compound has been used in treatment of CML that is resistant to another tyrosine kinase inhibitor, imatinib. It is also being investigated for use in treatment of Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), and dementia.
However, while nilotinib appears to be relatively safe, there are various serious side-effects and contraindications associated with its use. For example, nilotinib administration has been associated with severe cardiovascular issues, including hypertension, arrhythmia, and prolonged QT interval. Indeed, sudden deaths have been reported, associated with nilotinib. Contraindications for use of nilotinib include long QT syndrome, hypokalaemia, hypomagnesaemia, pregnancy, planned pregnancy, lactation, and galactose/lactose intolerance. Caution is also indicated for use in patients with myelosuppression, tumor lysis syndrome, history of pancreatitis, and total gastrectomy. Thus, while nilotinib finds suitable use in some patients, there remains a need for compounds for the safe treatment of CML.